IMPACT OF THE INHIBITION OF RENAL DOPAMINERGIC SYSTEM ON BLOOD PRESSURE AND INFLAMMATORY RESPONSE IN THE KIDNEY

Objective: Inhibition of peripheral dopa decarboxylase (DCAA) represents a pharmacological strategy for treatment of Parkinson’s disease, but its effects on kidney function and blood pressure (BP) are unknown. Our objective was to evaluate if chronic administration of carbidopa (Cb) could lead to renal inflammation and increase in BP levels. Design and method: Male Wistar Kyoto (WKY) rats were divided into two groups (n=8/group): WKY (drinking water) and WKY+Cb (Cb 25 mg/kg/day in drinking water). Similarly, spontaneously hypertensive rats (SHR) were divided into SHR and SHR+Cb groups. Chronic inhibition of renal dopaminergic system with Cb lasted 3 weeks. Systolic blood pressure (SBP) was measured weekly by the tail-cuff method. At the end of the treatment, we determined 24-hour fractional and urinary sodium excretion. Renal expression of Na+, K+–ATPase pump (NKA), dopaminergic D1-subtype and D2-subtype receptors (D1R and D2R), Parkinson’s protein 7 (PARK7) and nuclear factor kappa B (NF-kB) were determined by Western Blot. A p value <0.05 was considered significant (∗ versus WKY; # versus SHR). Results: At 3 weeks of treatment, Cb administration produced no changes in SBP levels (mmHg: WKY:118±4; WKY+Cb:115±3; SHR:228±8; SHR+Cb:237±6). Nonetheless, SBP levels were modified in the first week of treatment, with a greater increase observed in SHR+Cb versus SHR rats (mmHg: 240±3#; 210±10). A significant reduction in fractional and urinary sodium excretion was accompanied by an increase in renal NKA expression in SHR and WKY rats (arbitrary units, AU: WKY:1.00±0.08; WKY+Cb:1.30±0.14∗; SHR:1.30±0.23∗; SHR+Cb:1.78±0.13∗#). In the WKY+Cb group there was a significant decrease in D1R expression versus WKY group (AU: WKY:1.00±0.17; WKY+Cb:0.65±0.10∗) and a non-significant increase in D2R. PARK7 and NF-kB expression were unaltered in WKY+Cb and SHR+Cb rats versus corresponding groups without Cb. However, SHR+Cb group showed a greater expression of both markers compared to WKY group (AU PARK7: WKY:1.00±0.07; WKY+Cb:1.07±0.14; SHR:1.27±0.21; SHR+Cb:1.45±0.21∗) (AU NF-kB: WKY:1.00±0.11; WKY+Cb:1.12±0.16; SHR:1.22±0.07; SHR+Cb:1.36±0.18∗). Conclusions: Inhibition of renal dopamine synthesis with Cb alters tubular sodium handling, by increasing NKA expression and promoting greater sodium reabsorption. In the context of hypertension, these changes would be accompanied by a greater renal inflammatory response.